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Role of polymorphisms in TLR1 and PRKAA1 genes in the development of atrophic gastritis and gastric cancer
Leja, Mārcis | University of Latvia, Riga, Latvia | |
Link, Alexander | Otto-von- Guericke University Magdeburg, Magdeburg, Germany | |
Malfertheiner, Peter | Otto-von- Guericke University Magdeburg, Magdeburg, Germany | |
Date Issued |
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2017-09-07 |
Objective: Previous genome-wide association studies showed that genetic polymorphisms in TLR1 and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) were associated with gastric cancer (GC) or presence of Helicobacter pylori (H. pylori). The aim of this study was to evaluate associations between TLR1 and PRKAA1 genes polymorphisms and H. pylori infection, atrophic gastritis (AG) and GC. Methods: Single-nucleotide polymorphisms (SNPs) were analyzed in 1178 subjects (511 controls, 340 AG patients and 327 GC patients). TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. Results: We observed similar distribution of TLR1 and PRKAA1 genotypes in H. pylori positive and negative cases. Moreover, no significant differences in the frequencies of all polymorphisms between AG patients and controls were found. TC genotype of TLR1 gene was more prevalent in GC patients compared to control group (22.3% and 29.7% respectively, P=.018). TLR1 SNP was associated with increased risk of GC. Carriers of TC genotype had higher odds of GC when compared to TT genotype (OR – 1.89, 95% PI 1.26-2.83, P=.002). Similar association was observed in a dominant model for TLR1 gene, where comparison of CC+TC vs TT genotypes showed an increased risk of GC (OR – 1.86, 95% PI 1.26-2.75, P=.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed. Conclusions: TLR1 rs4833095 SNP is associated with increased risk of GC in population of European descent, while polymorphism in PRKAA1 gene is not linked with the presence of GC.